Nutlin-3 induces HO-1 expression by activating JNK in a transcription-independent manner of p53

CHOE, YUN-JEONG,LEE, SUN-YOUNG,KO, KYUNG WON,SHIN, SEOK JOON,KIM, HO-SHIK Spandidos Publications 2014 International journal of oncology Vol.44 No.3

A recent study reported that p53 can induce HO-1 by directly binding to the putative p53 responsive element in the HO-1 promoter. In this study, we report that nutlin-3, a small molecule antagonist of HDM2, induces the transcription of HO-1 in a transcription-independent manner of p53. Nutlin-3 induced HO-1 expression at the level of transcription in human cancer cells such as U2OS and RKO cells. This induction of HO-1 did not occur in SAOS cells in which p53 was mutated and was prevented by knocking down the p53 protein using p53 siRNA transfection, but not by PFT-alpha, an inhibitor of the transcriptional activity of p53. Accompanying HO-1 expression, nutlin-3 stimulated the accumulation of ROS and the phosphorylation of MAPKs such as JNK, p38 MAPK and ERK1/2. Nutlin-3-induced HO-1 expression was suppressed by TEMPO, a ROS scavenger, and chemical inhibitors of JNK and p38 MAPK but not ERK1/2. In addition, nutlin-3-induced phosphorylation of JNK but not p38 MAPK was inhibited by TEMPO. Notably, the levels of nutlin-3-induced ROS were correlated with the mitochondrial translocation of p53 and this induction was prevented by PFT-beta, an inhibitor of the mitochondrial translocation of p53. Consistent with the effect of the ROS scavenger and MAPK inhibitors, PFT-beta reduced HO-1 expression and the phosphorylation of JNK induced by nutlin-3. In the experiments of analyzing cell death, the knockdown of HO-1 augmented nutlin-3-induced apoptosis. Collectively, these results suggest that nutlin-3 induces HO-1 expression via the activation of both JNK which is dependent on ROS generated by p53 translocated to the mitochondria and p38 MAPK which appears to be stimulated by a ROS-independent mechanism, and this HO-1 induction may inhibit nutlin-3-induced apoptosis, constituting a negative feedback loop of p53-induced apoptosis.

Heme oxygenase-1 induced by desoxo-narchinol-A attenuated the severity of acute pancreatitis via blockade of neutrophil infiltration

Bae, Gi-Sang,Kim, Dong-Goo,Jo, Il-Joo,Choi, Sun-Bok,Kim, Myoung-Jin,Shin, Joon Yeon,Kim, Dong-Uk,Song, Ho-Joon,Joo, Myungsoo,Park, Sung-Joo ELSEVIER 2019 INTERNATIONAL IMMUNOPHARMACOLOGY Vol.69 No.-

<P><B>Abstract</B></P> <P>Heme oxygenase-1 (HO-1) has an anti-inflammatory action in acute pancreatitis (AP). However, its mechanism of action and natural compounds/drugs to induce HO-1 in pancreas are not well understood. In this study, we investigated the regulatory mechanisms of HO-1 during AP using desoxo-narchinol-A (DN), the natural compound inducing HO-1 in the pancreas. Female C57/BL6 Mice were intraperitoneally injected with supramaximal concentrations of cerulein (50 μg/kg) hourly for 6 h to induce AP. DMSO or DN was administered intraperitoneally, then mice were sacrificed 6 h after the final cerulein injection. Administration of DN increased pancreatic HO-1 expression through activation of activating protein-1, mediated by mitogen-activated protein kinases. Furthermore, DN treatment reduced the pancreatic weight-to-body weight ratio as well as production of digestive enzymes and pro-inflammatory cytokines. Inhibition of HO-1 by tin protoporphyrin IX abolished the protective effects of DN on pancreatic damage. Additionally, DN treatment inhibited neutrophil infiltration into the pancreas via regulation of chemokine (C-X-C motif) ligand 2 (CXCL2) by HO-1. Our results suggest that DN is an effective inducer of HO-1 in the pancreas, and that HO-1 regulates neutrophil infiltration in AP via CXCL2 inhibition.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Desoxo-narchinol-A (DN) is a natural compound of HO-1 inducer in pancreas. </LI> <LI> Mechanism of DN-induced HO-1 is mediated by MAPK/Activator Protein-1/HO-1 signaling. </LI> <LI> DN-induced HO-1 blocks neutrophil infiltration into pancreas via inhibition of CXCL2. </LI> <LI> DN inhibits cerulein-induced acute pancreatitis (AP) and AP-associated lung injury. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

병원단위의 임상진료지침 개발과정

신영수,김창엽,오병희,한규섭,윤병우,한준구,강영호 한국의료QA학회 1997 한국의료질향상학회지 Vol.4 No.1

Background : With increased concerns about variation among physician a practice pattern and their impact on the quality of care, clinical practice guidelines have been developed by many different organizations, with differing aims and incentives. From the same point of view, there is growing interest in the development of clinical practice guidelines in Korea, but with only a few examples. As a result, there is not much exploration on the incentive and barrier to development guidelines as well as description on the development process. The purposes of this study are to describe the process of the four different clinical practice guidelines in a hospital setting, and to identify incentives and barriers in the development of guidelines. Methods : For this research, a clinical practice guideline development committee and four clinical practice guideline development teams were organized in a university hospital which has more than 1,200 beds. Twenty eight doctors, three nurses, and one technician participated as members of development teams for eight months. Four to six meetings were held, and three to seven departments in the hospital were involved. Results : The topics which developed into clinical practice guidelines were cardiopulmonary resuscitation(CPR), blood transfusion, anticoagulation, and angiography. The main goals set by teams were education(CPR, angiography), risk management(blood transfusion), and to enhance quality of care(anticoagulation). Among four teams, only in the team for anticoagulation guideline medical record review and pilot-testing were performed. Also literature review was not carried out systematically. However, all the guidelines were developed by multidisciplinary participation by personnels of related departments. All the team expected guidelines to be used as standard protocols in the practice. Conclusion : Experience and skill in developing process has to be improved to have a more valid and useful practice guideline. In particular, literature review and problem identification by examining medical record should be emphasized. Also further studies of the clinical outcomes of the guidelines application and changes in physicians behaviors would be required.

심상성 루프스에서 Nested-Primer Gene Amplification Assay에 의한 결핵균 DNA의 검출

신문석,전효진,김병천,이규석,김재룡,권호준,송준영 啓明大學校 醫科大學 1994 계명의대학술지 Vol.13 No.4

Lupus vulgaris, which is a progressive form of postprimary tuberculosis in patients with a moderate to high degree of immunity and tuberculin sensitivity, is the most common, most serious, and most variable type of cutaneous and mucous membrane tuberculosis. Domonstration of M.tuberculosis directly or in culture in some of these eruptions can be difficult. It is essential to demonstrate the presence of M.tuberculosis in a clinical sample for a definitive diagnosis of tuberculosis. With the discovery of the polymerase chain reaction (PCR), the DNA diagnostic approach for infection has developed in a short period. With the dual purpose of definitive and rapid diagnosis of tuberculosis, this study examined the usefulness of a nested PCR for detection of M. turberculosis. Compared with a single-step PCR, the two-step PCR was able to enhance sensitivity approximately 1,000-fold on the basis of bacterial counts and DNA quantity. We concluded that two-step nested PCR appeared to be the most useful PCR protocol for early and sensitive diagnostic method detecting M.tuberculosis in acid-fast stain negative specimens.

무릎관절 추적훈련이 편마비 환자의 보행에 미치는 영향

신화경,염호준,조상현,장성호 한국전문물리치료학회 2003 한국전문물리치료학회지 Vol.10 No.3

무전해도금에 의한 다공성 니켈의 제조에 관한 연구

신준호,김기원,허보영 국립경상대학교 공과대학 부설 첨단소재연구소 1993 尖端素材 Vol.3 No.-

A new process on the preparation of porous nickel by electroless plating was developed using fine graphite powders of 1㎛-2㎛ particle diameter and polyurethane foam. In this process, graphite powders were introduced into the pores(foams) existing within polyurethane foam in order to supply electric conducting seeds for nickel deposition by electroless plating reaction. After the electroless plating, remaining polyurethane was removed chemically using organic solvent and most of graphite powder seeds also removed by ultrasonic cleaning. Porous nickel plates with 250㎛-300㎛ thickness and porosity comparable to commercial sintered nickel plate were obtained and found out that the platesare of mono-layer structure composed of spherical nickel particles connected each other in two-dimensional scale.

Ni-MH 전지용 thin nickel foam 의 제조

신준호,김기원 국립경상대학교 공과대학 부설 첨단소재연구소 1994 尖端素材 Vol.4 No.-

A new method for preparation of thin nickel foam for Ni-MH battery was tested. In this method, fine graphite powders with 1㎛-2㎛ diameter were pasted into pores of thin polyurethane, foam film in order to supply electric conducting seeds for nickel deposition by electroless plating reaction. After electroless plating, the nickel foam was electroplated and heat-treated to improve mechanical strength and ductility. During electroplating there was small amount of porosity decrease less than 5% up to 30㎛ coating thickness. Remaining polyurethane foam was removed chemically by organic solvent and free graphite particles also removed by ultra sonic cleaning. Finally, thin nickel foam with 350㎛-400㎛ thickness was obtained.

18S-srRNA 분석에 의한 Acantbamoeba 한국 분리주들의 분류 검토

신호준,지영진,조명수,김형일,박연희,임경일 아주대학교 의과학연구소 1998 아주의학 Vol.3 No.2

Acanthamoeba spp. spread in soil, ponds, air and swimming pool, cause a granulomatous amoebic meningitis and amoebic keratitis in human and experimental animals. Their classification had depended upon morphological characteristics and physiological conditions such as thermophilic status and generation times. However, because amoeba species showed the morphological and physiological diversity in isolates, many attempts have been made on identification of Acanthamoeba spp. Restriction fragments length polymorphism (RFLP) analysis of IBS-small subunit ribosomal RNA (srRNA) was an useful tool for classification among morphologically and genetically closely-related species. In this study, 18S-srDNAs of amoebae were amplified by PCR with primer encoding 18S-srRNA gene and digested with restriction endonudeases, and RFLP analysis was applied on classification of Acanthamoeba Korean isolates (YM-4, YM-5 and YM-7), comparing with reference amoebae, A. culbertsoni, A. polyphaga and A. royreba. Trophozoites of six Acanthamoeba spp. had typical acanthopoda, but did not show any morphological differences. Cyst of Acanthamoeba sp. YM-7 was similar to that of A. polyphaga which was designated as group Ⅱ Acanthamoeba. Morphologically other amoebae belonged to group Ⅲ Acanthamoeba. Digestion of 18S-srDNA with six enzymes, Dde Ⅰ, Hae Ⅲ, Hind Ⅲ, EcoR Ⅰ, Rsa Ⅰ and Sph Ⅰ, resulted in various DNA fragments. Using the method of Nei and U (1979) for RFLP analysis, genetic divergence was not observed between A culbertsoni and Acanthamoeba sp. YM-4. Between A. culbertsoni and Acanthamoeba sp. YM-5, genetic distance was 0.070, 0.364 between Acanthamoeba sp. YM-4 and A. polyphaga, and 0.277 between Acanthamoeba sp. YM-7 and A. polyphaga. In comparison with A. culbertsoni and A. polyphaga, Acanthamoeba sp. YM-7 showed genetic distance of 0.330 and 0.154, respectively. Thus, Acanthamoeba sp. YM-7 is a similar species to A. polyphaga. Acanthamoeba sp. YM-5 is a different species from A. polyphaga, but closely-related to A. culbertsoni. Acanthamoeba sp. YM-4 can be classified as a subspecies or a strain of A. culbertsoni.

기능성 고등어 Fillet 제조 및 저장 중 품질 변화

신석우,장미순,권미애,서호준 한국식품저장유통학회 ( 구 한국농산물저장유통학회 ) 2004 한국식품저장유통학회지 Vol.11 No.1

고등어 fillet 제품의 저장 중 항산화의 기능성을 부여하고 고등어 특유의 비린내를 제거하기 위해 식염 외에 녹차, dillweed, 키토산, 올리고당, 생강을 첨가하여 진공포장한 후 5℃, 0℃, -20℃에 80일간 저장하면서 제품 특성을 조사하였다. 5℃에 저장한 고등어 fillet의 휘발성 염기질소 측정 결과는 이들 첨가물을 단독 또는 복합적으로 첨가한 시제품에서 2주 이내에 초기부패에 도달했고, 0℃에서는 4∼7주, -20℃에서는 저장 80일간 모든 시제품에서 신선도를 유지할 수 있었다. 이들 첨가물 가운데서도 키토산과 올리고당을 첨가한 시제품이 가장 신선도가 양호함을 알 수 있었다. 항산화성은 초기 과산화물가가 5.4∼7.8 meq/kg 이었던 것이 5℃ 저장시 35일째 15.7∼20.4 meq.kg, 0℃저장시 49일째 13.9∼18.4 meq/kg, -20℃저장시 80일째 11.6∼20.2 meq/kg으로 저온 일수록 산화속도가 늦었고 각각의 저장온도에서도 녹차, dillweed, 생강, 키토산, 올리고당을 첨가한 시제품에서 가장 산화속도가 늦었다. 친유성 갈색도는 -20℃에서 80일간 저장기간동안 거의 변화가 보이지 않았고 5℃와 0℃에서는 저장기간이 연장됨에 따라 갈색도는 증가하는 경향을 나타내었다. 저장 중 생균수 변화는 5℃와 0℃에서는 저장 80일째까지 생균수 변화는 보이지 않아 신선도 유지가 가능하였다. 관능검사 결과는 5℃저장시 14∼21일, 0℃저장시 28∼49일 점질물이나 산패취가 발생하여 상품적 가치를 상실하였고, -20℃에서는 80일간 저장기간 동안에 이들 변화는 나타나지 않았다. In oredr to endow mackerel fillet with antioxidant effect, functionality and remove fishy smell, chitosan, oligosaccaide, extracts of green tea, dill weed and ginger was used as soaking solution additives. Quality characteristics of soaked mackerel fillet(SMF) was investigated during storage temperature and time after vacuum packing with polyvinyl chloride film. From the results of VBN measurement, initial spoilage was showed within 2 or 3 weeks in SMF soaked with brine including extracts of green tea, herb and ginger at 5℃. In case of adding chitosan and oligosaccarides to the solution mentioned above, initial spoilage was found from 4 to 7 weeks, oxidation was reduced remarkably and SMF stored at -20℃ maintained the freshness during 80 days. Viable cell counts were reached to 108 for 3 weeks storage at 5 and 0℃. But no change of viable cell counts was founded at -20℃. The shelf-lifes of SMF according to 5, 0 and -20℃ storage temperatures were 2 to 3, 4 to 7 weeks and about 3 months, respectively.

칼 바르트의 교회 교의학Ⅰ, 1권에서의 성령론

신준호 연세대학교 신과대학 2004 신학논단 Vol.35 No.-